Co-ingestion of Benzodiazepines and Opioids Contributes to Overdose and Death Interview with:
Christopher M. Jones, Pharm D., M.P.H
Senior advisor, Office of Public Health Strategy and Analysis
Office of the Commissioner, Food and Drug Administration

Medical Research: What is the background for this study?

Dr. Jones: Opioid analgesics and benzodiazepines are the two most common drug classes involved in prescription drug overdose deaths. In 2010, 75% of prescription drug overdose deaths involved opioid analgesics and 29% involved benzodiazepines. Opioid analgesics and benzodiazepines are also the most common drugs associated with emergency department visits due to nonmedical use of prescription drugs.

Combined opioid and benzodiazepine use has been suggested as a risk factor for overdose death.

Opioids and benzodiazepines have complex drug interactions and in combination can result in synergistic respiratory depression, but the exact mechanisms by which benzodiazepines worsen opioid-related respiratory depression are not fully understood.

Widespread co-use of benzodiazepines and opioids has been documented in both chronic pain and addiction treatment settings. Studies suggest that among patients who receive long-term opioids for chronic non-cancer pain, 40% or more also use benzodiazepines. Among patients who abuse opioids, benzodiazepine abuse also is prevalent, and co-users report using benzodiazepines to enhance opioid intoxication.

This study builds on the prior literature by analyzing trends on how the combined use of opioids and benzodiazepines in the U.S. contributes to the serious adverse outcomes of nonmedical use–related ED visits and drug overdose deaths. A better understanding of the consequences of co-use of these medications will help identify at-risk populations, inform prevention efforts, and improve the risk–benefit balance of these medications.

Medical Research: What are the main findings?

Dr. Jones: From 2004 to 2011, the rate of nonmedical use–related Emergency Department visits involving both opioid analgesics and benzodiazepines increased from 11.0 to 34.2 per 100,000 population. During the same period, drug overdose deaths involving both drugs increased from 0.6 to 1.7 per 100,000. Statistically significant increases in Emergency Department visits occurred among males and females, non-Hispanic whites, non-Hispanic blacks, and Hispanics, and all age groups except 12–17-year-olds. For overdose deaths, statistically significant increases were seen in males and female, all three race/ethnicity groups, and all age groups except 12–17-year-olds. Benzodiazepine involvement in opioid analgesic overdose deaths increased each year, increasing from 18% of opioid analgesic overdose deaths in 2004 to 31% in 2011.

Medical Research: What should clinicians and patients take away from your report?

Dr. Jones: This study describes the increasing public health burden of opioid analgesic and benzodiazepine co-ingestion. Interventions to reduce morbidity and mortality from the co-ingestion of these drugs will require a multifaceted approach, including prescriber education, state-level policies, and enforcement practices that hold providers accountable for appropriate prescribing; federal regulatory actions that improve safe use of these medications; community-level prevention; and coordinated treatment for pain, mental health, and substance use disorders, which often co-occur. Raising provider and public awareness is an important step toward the advancement of policies and programs designed to achieve a better balance between the benefits and risks associated with these medications.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Jones: More research is needed to better understand patterns and trends in benzodiazepine prescribing—and particularly co-prescribing with opioids—and to assess the effectiveness of strategies to reduce inappropriate co-prescribing and co-use of these drugs. Further research is needed to examine use, abuse, and overdose associated with specific opioids and benzodiazepines and combinations; the role of alternate routes of administration; and the potential for abuse-deterrent technologies to reduce opioid–benzodiazepine abuse and its adverse health consequences.

HHS Secretary Sylvia M. Burwell has made addressing opioid abuse, dependence, and overdose a priority and work is underway within HHS on this important issue. The evidence-based initiative focuses on three promising areas: informing opioid prescribing practices, increasing the use of naloxone – a drug that reverses symptoms of a drug overdose, and using medication-assisted treatment to slowly move people out of opioid addiction.

The Obama Administration is also committed to tackling the prescription drug and heroin epidemic, proposing significant investments to intensify efforts to reduce opioid misuse and abuse.


Am J Prev Med. 2015 Jul 2. pii: S0749-3797(15)00163-4. doi: 10.1016/j.amepre.2015.03.040. [Epub ahead of print]

Emergency Department Visits and Overdose Deaths From Combined Use of Opioids and Benzodiazepines.

Jones CM1, McAninch JK2.

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Christopher M. Jones, Pharm D., M.P.H (2015). Co-ingestion of Benzodiazepines and Opioids Contributes to Overdose and Death 

Last Updated on November 4, 2015 by Marie Benz MD FAAD